Role of CD8 beta domains in CD8 coreceptor function: Importance for MHC I binding, signaling, and positive selection of CD8(+) T cells in the thymus

The contribution of the CDB beta subunit to CD8 coreceptor function is poor ly understood. We now demonstrate that the CD8 beta extracellular domain in creases the avidity of CD8 binding to MHC I, and that the intracellular dom ain of CD8 beta enhances association with two intracellular molecules requi red for TCR signal transduction, Lck and LAT. By assessing CD8(+) T cell di fferentiation in CD8 beta-deficient mice reconstituted with various transge nic CD8 beta chimeric molecules, we also demonstrate that the intracellular and extracellular domains of CD8 beta can contribute independently to CD8( +) T cell development, but that both CD8 beta domains together are most eff icient. Thus, this study identifies the molecular functions of the CD8 beta intracellular and extracellular domains and documents their contributions to CD8(+) T cell development.